Preschool Scale Research Articles

Music@Home–Retrospective: A new measure to retrospectively assess childhood home musical environments

Early home musical environments can significantly impact sensory, cognitive, and socioemotional development. While longitudinal studies may be resource-intensive, retrospective reports are a relatively quick and inexpensive way to examine associations between early home musical environments and adult outcomes. We present the Music@Home–Retrospective scale, derived partly from the Music@Home–Preschool scale (Politimou et al., 2018), to retrospectively assess the childhood home musical environment. In two studies (total n = 578), we conducted an exploratory factor analysis (Study 1) and confirmatory factor analysis (Study 2) on items, including many adapted from the Music@Home–Preschool scale. This revealed a 20-item solution with five subscales. Items retained for three subscales (Caregiver Beliefs, Caregiver Initiation of Singing, Child Engagement with Music) load identically to three in the Music@Home-–Preschool Scale. We also identified two additional dimensions of the childhood home musical environment. The Attitude Toward Childhood Home Musical Environment subscale captures participants’ current adult attitudes toward their childhood home musical environment, and the Social Listening Contexts subscale indexes the degree to which participants listened to music at home with others (i.e., friends, siblings, and caregivers). Music@Home–Retrospective scores were related to adult self-reports of musicality, performance on a melodic perception task, and self-reports of well-being, demonstrating utility in measuring the early home music environment as captured through this scale. The Music@Home–Retrospective scale is freely available to enable future investigations exploring how the early home musical environment relates to adult cognition, affect, and behavior.

Childhood exposure to pyrethroids and neurodevelopment in Canadian preschoolers

BackgroundPyrethroid insecticides are used both residentially and agriculturally and their toxicity targets the nervous system of insects. They might also interfere with development and function of the human brain. A few epidemiological studies suggest that exposure to pyrethroids may be associated with neurobehavioral problems in children but there is little data on potential associations with cognitive outcomes. Furthermore, many studies showed that the neurotoxic effects of several pesticides are modified by sex, hence, considerations of potential sex-differences are important to investigate. ObjectiveTo study the cross-sectional association between urinary levels of pyrethroid metabolites and neurodevelopment, including neurobehavioral and cognitive outcomes, in preschool-age children, and to examine whether sex might modify these associations. MethodsWe used data from a follow-up examination of the Maternal-Infant Research on Environmental Chemicals (MIREC), the MIREC Child Development study (MIREC-CD Plus) on children at age 3–4 years living in 6 Canadian cities. For each participant, we collected a urine sample for measurements of pyrethroids metabolites (cis-DBCA, cis-DCCA, trans-DCCA, 3-PBA, 4-F-3-PBA). We assessed neurodevelopment with the Wechsler Primary and Preschool Scale of Intelligence–III (WPPSI-III) and two scales of the Behavior Rating Inventory of Executive Function–Preschool (BRIEF-P). Parents reported children’s behavior using the Behavior Assessment System for Children–2 (BASC-2) and the Social Responsiveness Scale-2 (SRS-2). We examined associations between children’s urinary pyrethroid metabolite concentrations and neurodevelopmental scores with multiple linear regression models, adjusting for confounders, in boys and girls separately. ResultsThe study included 179 children (mean age: 3.2 y, range 2.8–4.0). The detection frequencies were high for most pyrethroid metabolites (83–100%), but lower for 4-F-3-PBA (36%). Higher concentrations of cis-DBCA were significantly associated with lower verbal, performance and full-scale IQ scores in boys (e.g., for a 2-fold increase in cis-DBCA, β = −2.0; 95% CI: −3.4, −0.6 for full-scale IQ). In girls, the only metabolite associated with cognitive scores was 3-PBA, which was associated with lower verbal IQ scores (β = −1.3, 95% CI: −2.6, −0.1). For neurobehavioral outcomes in boys, there were associations between poorer BASC-2 Adaptive Skills scores with higher concentrations of cis-DCCA (β = −1.6, 95% CI: −2.3, −0.9), trans-DCCA (β = −1.5, 95% CI: −2.2, −0.8), 3-PBA (β = −1.7, 95% CI: −2.5, −0.9), and sum of pyrethroid metabolites (β = −1.8, 95% CI: −2.6, −0.9). In girls, we observed a significant association between higher concentration of cis-DCCA and better BASC-2 Adaptive Skills score (β = 1.0; 95% CI, 0.2, 1.8), but not with other urinary pyrethroids metabolites. Scores on the SRS-2 and BRIEF-P were not associated with pyrethroid metabolites. ConclusionThere were associations between some pyrethroid pesticide metabolites and indicators of neurodevelopmental disorder, especially among boys. These associations are in agreement with previous studies and could suggest that exposure to pyrethroid pesticides represents a risk of potential toxicity for the cognitive development of children, and a risk for behavioral development. However, the cross-sectional nature of this study limits causal inferences.

0490 Longitudinal associations between sleep and behavior and cognition in preschoolers from five European birth-cohorts

Abstract Introduction There has been little focus on sleep and its relation to behavior and cognition in preschool-aged children. We aimed to investigate the association between sleep duration in early preschoolers (» 3.5 years of age) and later behavioral and cognitive outcomes (» 5 years of age) in European children. Methods We used harmonized data from five cohorts from the EU Child Cohort Network, established by the LifeCycle Project (n=16.444 children): ALSPAC and SWS from UK, EDEN and ELFE from France and INMA from Spain. Within all cohorts, total sleep duration per day and behavioral and cognitive information were reported by parents. Internalizing and externalizing behaviors were measured with the Strengths and Difficulties Questionnaire and treated as percentile scores. Verbal and non-verbal intelligence were assessed by the Wechsler Preschool and Primary Scale of Intelligence or with the McCarthy Scales of Children’s Abilities depending on the cohort and treated as standardized scores. All scores were cohort specific. Associations between sleep duration during early preschool age and later behavior and/or cognition were estimated using linear regression and pooled with two-stage individual participant data meta-analysis adjusted for child, maternal and household information. Analyses were done in DataSHIELD. Results Global mean sleep duration was 11h54 ± 1h00 per day at mean age 3.5 years but differed by country, with children from France showing longer sleep duration than children from the UK or Spain. In multivariate meta-analysis, 1 hour of additional sleep duration per day at mean age 3.5 years was associated with reduced internalizing and externalizing behavior percentile scores at mean age 5.1 years (internalizing behavior: badjusted= -1.05, 95%-CI [-1.93, -0.18], I2: 30.3%; externalizing behavior: badjusted= -2.12, 95%-CI [-2.78, -1.47], I2: 0.0%). No association was observed between sleep duration and subsequent verbal or non-verbal intelligence Conclusion Longer sleep duration in early preschool age (» 3.5 years of age) was associated with subsequent lower internalizing and externalizing behavior scores (» 5 years of age), but not with verbal or non-verbal intelligence. Adequate sleep duration at an early age is important for children’s later mental health. Support (If Any) KG was granted a LifeCycle fellowship.

The Role of Cognitive Skills, Sex, and Parental Education for Social-Emotional Skills: A Cross-Sectional Study on the WPPSI-IV Performances of Children Aged 3 to 5 Years.

Background: Current research suggests that knowledge about the relationship between cognition and social–emotional skills in preschoolers is important to better understand child development. The present study investigated possible effects of cognitive skills measured by the Wechsler Primary and Preschool Scale—Fourth Edition (WPPSI-IV), children’s sex, and parental educational level on social–-emotional skills measured by the Developmental Test 6 Months to 6 Years—Revision (ET 6-6 R) for children aged 3 to 5. Methods: Statistical analyses were based on a sample of N = 93 children (47 females, 46 males). First, bivariate correlations among relevant WPPSI-IV index scores, the ET social–emotional quotient, children’s sex, and parental educational level were calculated to identify possible significant associations between the variables under investigation. Subsequently, two multiple regression analyses were conducted to test for the hypothesized main effects of cognitive skills, children’s sex, and parental educational level on social–emotional skills. Finally, a moderated multiple regression analysis was carried out to investigate whether possible effects of cognitive skills on social–emotional skills were moderated by children’s sex and parental educational level. Results: Regression analyses indicated that visual–spatial skills measured by the WPPSI-IV and children’s sex have both a small but significant main effect on social–emotional skills. The main effect of sex was due to the fact that, on average, females achieved higher scores on the measure of social–emotional skills than males. Conclusions: The present findings suggest that the WPPSI-IV represents a suitable test battery for the assessment of those cognitive skills, which might play a reasonable role in social–emotional development

Cardiovascular Health at Age 5 Years: Distribution, Determinants, and Association With Neurodevelopment.

BackgroundEarly childhood may represent an opportune time to commence primordial prevention of cardiovascular disease (CVD, i.e., prevention of risk factors onset), but epidemiological evidence is scarce. We aimed to examine the distribution and parental and early life determinants of ideal cardiovascular health (CVH) in children up to 5 years and to compare the level of cognitive development between children with and without ideal CVH at age 5 years.MethodsUsing data from the Etude sur les déterminants pré et post natals précoces du Développement psychomoteur et de la santé de l'Enfant (EDEN) study, a French population-based mother–child cohort study, CVH was examined in children at 5 years of age based on the American Heart Association CVH metrics (ideal body mass index, physical activity, diet, blood pressure, cholesterol and glucose levels, and passive smoking, considered in sensitivity analysis only). Children were categorized as having ideal (five to six ideal metrics) or non-ideal CVH (<5 ideal metrics). Intelligence quotient (IQ) at age 5 years was assessed using the French version of the Wechsler Preschool and Primary Scale of Intelligence.ResultsAmong the 566 children (55% boys), only 34% had ideal CVH. In fully adjusted logistic regression, boys compared to girls (OR = 1.77, 95% CI 1.13–2.78), children with intermediate (1.77, 1.05–2.98) or ideal (2.58, 1.38–4.82) behavioral CVH at age 3 years and children who spent < 30 min/day watching television (1.91, 1.09–3.34) at age 3 years were more likely to have ideal CVH at age 5 years. At age 5 years, there was a significant 2.98-point difference (95% CI 0.64–5.32) in IQ between children with and without ideal biological CVH after adjusting for confounders.ConclusionThis study highlights that only a third of children aged 5 years had ideal CVH and identified modifiable determinants of ideal CVH and is suggestive of an association between CVH and neurodevelopment at a young age.

Perinatal, neonatal, developmental and demographic predictors of intelligence at 4\xa0years of age among low birth weight children: a panel study with a 2-year follow-up

IntoductionChildhood intelligence is an important predictor of later outcomes in life such as socioeconomic status or health. Hence, a deeper understanding of predictors of child intelligence should suggest points of intervention for children facing adversities.ObjectivesThe purpose of this study is to examine the predictive value of demographic, perinatal and neonatal variables after birth and developmental characteristics at age 2 for 4-year intelligence as outcome among low birth weight children.MethodsWe designed a panel study with a 2-year follow-up with 114 child-mother pairs. The outcome variable was IQ intelligence quotient at 4 years of age of LBW low birth weight children measured by the Wechsler Primary and Preschool Scales of Intelligence. Potential predictors were maternal education, family wealth, ethnic identity; sex, twin pregnancy, gestational age, birth weight, Apgar scores, maternal smoking during pregnancy; diagnosis of intravetricular haemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia after birth and cognitive, language and motor development at age 2 measured by one composite score of the three Bayley Scales of Infant and Toddler Development aggregated.ResultsStepwise backward regression was carried out including significant variables from the bivariate analysis. The best model included 4 predictors which accounted for 57% of the variance of the full IQ intelligence at 4-years of age. Maternal higher education was significant positive, below average family wealth and neonatal diagnosis of bronchopulmonary dysplasia were significant negative predictors in the model after birth. 2-year developmental characteristics such as cognitive, motor and language skills were positive predictors of the IQ intelligence at age 4.ConclusionSociodemographic assessment at birth and developmental assessment at two years of age are of crucial importance to recognize children at high risk for delayed cognitive development. High-risk children should be directed to supportive interventions and their development should be regulary monitored.

Cognitive profiles in children and adolescents with Down syndrome

The Down syndrome (DS) phenotype is usually characterized by relative strengths in non-verbal skills and deficits in verbal processing, but high interindividual variability has been registered in the syndrome. The goal of this study was to explore the cognitive profile, considering verbal and non-verbal intelligence, of children and adolescents with DS, also taking into account interindividual variability. We particularly aimed to investigate whether this variability means that we should envisage more than one cognitive profile in this population. The correlation between cognitive profile and medical conditions, parents’ education levels and developmental milestones was also explored. Seventy-two children/adolescents with DS, aged 7–16 years, were assessed with the Wechsler Preschool and Primary Scale of Intelligence-III. Age-equivalent scores were adopted, and Verbal and Non-Verbal indices were obtained for each individual. The cognitive profile of the group as a whole was characterized by similar scores in the verbal and non-verbal domain. Cluster analysis revealed three different profiles, however: one group, with the lowest scores, had the typical profile associated with DS (with higher non-verbal than verbal intelligence); one, with intermediate scores, had greater verbal than non-verbal intelligence; and one, with the highest scores, fared equally well in the verbal and non-verbal domain. Three cognitive profiles emerged, suggesting that educational support for children and adolescents with DS may need to be more specific.

Study protocol: childhood outcomes of fetal genomic variants: the PrenatAL Microarray (PALM) cohort study

BackgroundThe implementation of genomic testing in pregnancy means that couples have access to more information about their child’s genetic make-up before birth than ever before. One of the resulting challenges is the management of genetic variations with unclear clinical significance. This population-based study will help to close this critical knowledge gap through a multidisciplinary cohort study of children with and without genomic copy number variants (CNVs) diagnosed before birth. By comparing children with prenatally-ascertained CNVs to children without a CNV, we aim to (1) examine their developmental, social-emotional and health status; (2) measure the impact of prenatal diagnosis of a CNV on maternal perceptions of child health, behavior and development; and (3) determine the proportion of prenatally-ascertained CNVs of unknown or uncertain significance that are reclassified as benign or pathogenic after 2 or more years.MethodsThis study will establish and follow up a cohort of mother-child pairs who have had a prenatal diagnosis with a chromosomal microarray from 2013-2019 in the Australian state of Victoria. Children aged 12 months to 7 years will be assessed using validated, age-appropriate measures. The primary outcome measures will be the Wechsler Preschool and Primary Scale of Intelligence IV (WPSSI-IV) IQ score (2.5 to 7 year old’s), the Ages and Stages Questionnaire (12-30 months old), and the Brief Infant- Toddler Social and Emotional Assessment (BITSEA) score. Clinical assessment by a pediatrician will also be performed. Secondary outcomes will be scores obtained from the: Vineland Adaptive Behavior Scale, Maternal Postnatal Attachment Questionnaire, the Vulnerable Child Scale, Profile of Mood States, Parent Sense of Competence Scale. A descriptive analysis of the reclassification rates of CNVs after ≥2 years will be performed.DiscussionThis study protocol describes the first Australian cohort study following children after prenatal diagnostic testing with chromosomal microarray. It will provide long-term outcomes of fetal genomic variants to guide evidence-based pre-and postnatal care. This, in turn, will inform future efforts to mitigate the negative consequences of conveying genomic uncertainty during pregnancy.Trial registrationACTRN12620000446965p; Registered on April 6, 2020.

A randomized EPIREMED protocol study on the long-term visuo spatial effects of very preterm children with a working memory deficit

BackgroundVery preterm children generally perform poorly in executive functions and particularly in working memory. Adaptive training tasks encouraging these children to work continuously on their personal working memory capacity can be very useful. Above all in preschool-age children, several cognitive training programs focused on improving working memory capacity. Cogmed is a computerized visuospatial cognitive training program that improves working memory in children and adolescents with attention-deficit/hyperactivity disorder. The main objective is to assess the long-term effects (18 months) of cognitive training (Cogmed) on visuospatial processing in preschool-age very preterm children with working memory impairment.MethodsThe EPIREMED study is a prospective, randomized, controlled, multicentric trial nested in a population based epidemiological survey. An intervention group (Cogmed cognitive training) and a control group (standard care management) will compare children aged 5½ to 6 years, born between 24- and 34-weeks’ gestational age, with a global intelligence quotient > 70 and a working memory index < 85. The study will include 166 children from national study EPIPAGE-2 (Epidemiological Study on Small Gestational Ages). The intervention consists of 25 sessions administered over a 5- to 8-week period. The primary endpoint will be the visuospatial processing, assessed by the score of the visuospatial index: score of the WPPSI-IV (Wechsler Preschool and Primary Scale of Intelligence). The secondary endpoints will allow to assess the executive functions, language and abilities, infant behavior, quality of life assessment, school performance and parental anxiety.DiscussionThis project’s primary goal is to demonstrate the necessity of early visuospatial memory assessment within the vulnerable population of very preterm children, and to prove the feasibility and efficacy of computerized cognitive training using online software programs. A better global neuropsychological development improvement (visuospatial processing and other far transfer) can be expected with an improvement in learning and decreased behavioral problems. In the long term, these improvements might also reduce those global costs linked to the consequences of extreme prematurity.Trial registrationNCT02757794 (registered on 2nd May 2016 at ClinicalTrial.gov).

A National Comparative Investigation of Twins With Congenital Heart Defects for Neurodevelopmental Outcomes and Quality of Life (Same Same, but Different?): Protocol for a Prospective Observational Study.

BackgroundDue to the increased survival rates of patients with congenital heart defects (CHD), associated disorders are an increasing focus of research. Existing studies figured out an association between CHD and its treatment, and neurodevelopmental outcomes including motor competence impairments. All these studies, however, compared their test results with reference values or results of healthy control groups. This comparison is influenced by socioeconomic and genetic aspects, which do have a known impact on neurodevelopmental outcomes.ObjectiveThis study protocol describes a setting that aims to find out the role of CHD and its treatments on neurodevelopmental outcomes, excluding socioeconomic and genetic aspects. Only a twin comparison provides the possibility to exclude these confounding factors.MethodsIn a German-wide prospective cohort study, 129 twin siblings registered in the National Register for Congenital Heart Defects will undergo testing on cognitive function (Wechsler Intelligence Tests age-dependent: Wechsler Adult Intelligence Scale, fourth edition; Wechsler Intelligence Scale for Children, fifth edition; and Wechsler Preschool and Primary Scale of Intelligence, fourth edition) and motor competence (Movement Assessment Battery for Children, second edition). Additionally, the self-reported health-related quality of life (KINDL-R for children, Short Form 36 for adults) and the parent-reported strength and difficulties of the children (Strength and Difficulties Questionnaire, German version) will be assessed by standardized questionnaires. CHD data on the specific diagnosis, surgeries, transcatheter procedures, and additional medical information will be received from patient records.ResultsThe approval of the Medical Ethics Committee Charité Mitte was obtained in June 2018. After getting funded in April 2019, the first enrollment was in August 2019. The study is still ongoing until June 2022. Final results are expected in 2022.ConclusionsThis study protocol provides an overview of the study design’s technical details, offering an option to exclude confounding factors on neurodevelopmental outcomes in patients with CHD. This will enable a specific analysis focusing on CHD and clinical treatments to differentiate in terms of neurodevelopmental outcomes of patients with CHD compared to twin siblings with healthy hearts. Finally, we aim to clearly define what is important to prevent patients with CHD in terms of neurodevelopmental impairments to be able to develop targeted prevention strategies for patients with CHD.Trial RegistrationGerman Clinical Trials Register DRKS00021087; https://tinyurl.com/2rdw8w67International Registered Report Identifier (IRRID)DERR1-10.2196/26404

Investigation of the Problematic Behaviors of Preschool Students Studying in Public and Private Schools

This study was conducted to investigate the problematic behaviors of preschool students studying in public and private schools according to certain variables. The research was carried out with 300 students and their parents in private and public kindergartens. A demographic information form prepared by the researcher was used to collect the data. The Preschool and Kindergarten Behavior Scale was used. Pearson Correlation Analysis was used to analyze the data obtained for behavioral problems and social skills, univariate t-test for the significance of the difference between the scale scores of the groups by one-way analysis of variance, and the result was a significant negative relationship between problem behaviors and social skills. Significant differences were observed between students’ age, number of siblings, birth order, media usage, private or state education, their parent’s marital status, their family’s level of education and economic status, size of family, and students’ behavior problems and social skills sub-dimensions. However, no significant difference was observed regarding the gender of the children.

Stimulation and cognitive function in short-stature preschoolers

Background Normal-height children generally have better cognitive function than growth-stunted, short-stature children. Children’s cognitive function reportedly improves with stimulation. However, a correlation between stimulation and cognitive function in children with a history of short stature remains unclear.&#x0D; Objective To assess correlation between stimulation and cognitive function in normal-height vs. short-stature preschool children.&#x0D; Methods A cross-sectional study with consecutive sampling was performed in four sub-district areas in Jakarta. Preschool-aged children and their primary caregivers from previous studies on short stature were eligible for inclusion. An Indonesian version of a questionnaire was used to assess stimulation. A psychologist assessed verbal IQ (VIQ), performance IQ (PIQ), and full-scale IQ (FSIQ) with the Indonesian version of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI). Data were analyzed using Pearson’s correlation and Chi-square tests, and P values &lt;0.05 were considered to be significant.&#x0D; Results Of 62 subjects, 64.5% had normal height and 35.5% had short stature. Both normal-height and short-stature children had similar IQ outcome and history of stimulation. The stimulation was significantly correlated with FSIQ in normal-height children (r= 0.316; P=0.047), but not short-stature children (r=0.049; P=0.828). However, the percentage differences in VIQ, PIQ, and FSIQ between normal-height and short-stature children were not significant (P=0.409, 0.119 and 0.877, respectively).&#x0D; Conclusion There is a significant correlation between stimulation and IQ in normal-height children. Short-stature preschoolers were not worse in terms of IQ than normal-height preschoolers. Parents and caregivers should be encouraged to provide regular and adequate stimulation to their young children.

The performance of children with intellectual giftedness and intellectual disability on the WPPSI-IVA&NZ

ABSTRACT Objective The Wechsler Preschool and Primary Scale of Intelligence – Fourth Edition Australian and New Zealand Standardised Edition (WPPSI-IVA&NZ) is one of the most widely used intelligence assessments for children aged 2 years 6 months to 7 years 7 months. Given the impact of clinical and placement decisions that are supported by WPPSI-IVA&NZ results, it is important to provide evidence of criterion-related validity. Criterion-related validity refers to the degree to which test scores are associated with an external criterion (e.g., pre-existing diagnosis or classification). Method Two studies of children with intellectual giftedness (n = 19) and intellectual disability (n = 15) were conducted to determine if the constructs measured by the WPPSI-IVA&NZ perform as expected in criterion groups with known characteristics. Results Independent sample t-tests revealed mean composite scores for intellectually gifted children were significantly higher than matched controls, with the exception of the Processing Speed Index and Cognitive Proficiency Index. Children with intellectual disability on average obtained significantly lower mean scores on all composites relative to matched controls. Conclusion Results indicated that the WPPSI-IVA&NZ can provide valid estimates of intellectual ability for children with intellectual giftedness and intellectual disability that align with their previous diagnosis or classification.

Sex Differences in Intelligence in Children Aged 2:6–7:7: Analysis of the Factor Structure and Measurement Invariance of the German Wechsler Primary and Preschool Scale of Intelligence–Fourth Edition

The present study investigated gender differences in cognitive abilities for children aged 2–7 years on the German Wechsler Primary and Preschool Scale of Intelligence–Fourth Edition (WPPSI-IV). WPPSI-IV data of 1,042 children (517 girls and 525 boys) were selected from the extended dataset of the German WPPSI-IV standardization sample. First of all, confirmatory factor analyses (CFAs) were used to verify the factor structure of the WPPSI-IV, which was proposed by the test developers. Then, multiple-group confirmatory factor models were implemented to explore measurement invariance across gender. Finally, mean differences in the subtests, index scores, as well as full scale IQ (FSIQ) were analyzed. The second-order three-factor model for age group 2:6–3:11 as well as the second-order five-factor model for age group 4:0–7:7 could be verified. For age group 2:6–3:11, full scalar invariance could be accepted, whereas partial scalar invariance could be established by freeing five nonequivalent subtest intercepts for age group 4:0–7:7. These findings support interpretable comparisons of the WPPSI-IV scores between girls and boys. For age group 4:0–7:7, partial invariance should be taken into account in these comparisons. Furthermore, girls aged 4:0–7:7 showed an advantage in processing speed (PS). Mean scores in any of the other cognitive abilities did not differ between girls and boys in both age groups. These results indicated measurement invariance across gender on the WPPSI-IV, so that the tests measure cognitive abilities in the same way for girls and boys. The current findings showed that gender differences in PS may emerge in early childhood, which might lead to gender differences in later educational skills.

Long-Term Neurodevelopmental Outcome of Children after in Utero Exposure to Chemotherapy

Simple SummaryFacing cancer diagnosis during pregnancy constitutes a truly complex and challenging situation for both the patients and the physicians. Cancer diagnosis in a period of hope and joy is an unendurable situation that may affect the psychosocial functioning of the mother, causing depression, anxiety, self-blame, and social isolation. At the same time, a moral dilemma evolves among medical professionals; what is best for the mother in terms of immediate chemotherapy may have detrimental effects on the fetus, and conversely, delaying therapy and protecting the fetus may have a negative impact on the mother as the tumor progresses. Solid data on the safety profile or risks of anti-cancer agents and on the long-term neurodevelopmental outcome of children after in utero exposure to chemotherapy may provide both the patients and the physicians the information necessary for shared decision making when cancer is diagnosed during pregnancy.Pregnancy-related cancer management represents a real challenge for both the patients and the physicians. The long-term neurodevelopmental outcome of children in utero exposed to chemotherapeutic agents has only recently been addressed. This review aims to systematically integrate and highlight all existing data from the literature regarding the effect of prenatal exposure to chemotherapy on fetal brain growth and child development. All eligible studies are based on validated neurodevelopmental testing scales (e.g., Bayley Scales of Infant Development, Wechsler Preschool and Primary Scale of Intelligence) and/or well-defined questionnaires. Our systematic review including 17 studies demonstrates that no major consequences on the neurodevelopment of children after in utero exposure to anti-cancer drugs have been reported; nevertheless, longer and more thorough follow-up with large-scale multicenter prospective studies is certainly required in order to draw firm conclusions.

Location and Size of Preterm Cerebellar Hemorrhage and Childhood Development

To examine the association between cerebellar hemorrhage (CBH) size and location and preschool-age neurodevelopment in very preterm neonates. Preterm magnetic resonance images of 221 very preterm neonates (median gestational age = 27.9 weeks) were manually segmented for CBH quantification and location. Neurodevelopmental assessments at chronological age 4.5 years included motor (Movement Assessment Battery for Children, 2nd Edition [MABC-2]), visuomotor integration (Beery-Buktenica Developmental Test of Visual-Motor Integration, 6th Edition), cognitive (Wechsler Primary and Preschool Scale of Intelligence, 3rd Edition), and behavioral (Child Behavior Checklist) outcomes. Multivariable linear regression models examined the association between CBH size and 4.5-year outcomes accounting for sex, gestational age, and supratentorial injury. Probabilistic maps assessed CBH location and likelihood of a lesion to predict adverse outcome. Thirty-six neonates had CBH: 14 (6%) with only punctate CBH and 22 (10%) with ≥1 larger CBH. CBH occurred mostly in the inferior aspect of the posterior lobes. CBH total volume was independently associated with MABC-2 motor scores at 4.5 years (β = -0.095, 95% confidence interval = -0.184 to -0.005), with a standardized β coefficient (-0.16) that was similar to that of white matter injury volume (standardized β = -0.22). CBH size was similarly associated with visuomotor integration and externalizing behavior but not cognition. Voxelwise odds ratio and lesion-symptom maps demonstrated that CBH extending more deeply into the cerebellum predicted adverse motor, visuomotor, and behavioral outcomes. CBH size and location on preterm magnetic resonance imaging were associated with reduced preschool motor and visuomotor function and more externalizing behavior independent of supratentorial brain injury in a dose-dependent fashion. The volumetric quantification and localization of CBH, even when punctate, may allow opportunity to improve motor and behavioral outcomes by providing targeted intervention. ANN NEUROL 2020;88:1095-1108.

Associations of birth size, infancy, and childhood growth with intelligence quotient at 5 years of age: a Danish cohort study

ABSTRACTBackgroundThe correlates of prenatal and postnatal growth on Intelligence Quotient (IQ) in childhood in term-born children living in high-income countries are not well known.ObjectivesWe examined how birth size and growth in infancy and childhood were associated with IQ at age 5 y in term-born children using path analysis.MethodsThe study sample comprised 1719 children from the Danish National Birth Cohort who participated in a substudy in which psychologists assessed IQ using the Wechsler Primary and Preschool Scales of Intelligence–Revised. Measured weight, length/height, and head circumference at birth, 5 mo, 12 mo, and 5 y were included in a path model to estimate their total, indirect, and direct effects on IQ. All growth measures were included in the model as sex- and age-standardized z-scores.ResultsAfter adjusting for potential confounders, a positive association between birth weight and IQ was observed, and 88% of the association was direct. Weight gain in infancy was associated with IQ [per z-score increase from 5 to 12 mo, IQ increased by 1.53 (95% CI: 0.14; 2.92) points] whereas weight gain from 12 mo to 5 y was not associated with IQ. Height and head circumference growth in childhood was associated with IQ [per z-score increase from 12 mo to 5 y, IQ increased by 0.98 (95% CI: 0.17; 1.79) and 2.09 (95% CI: 0.78; 3.41) points, respectively].ConclusionsIn children born at term in an affluent country with free access to health care, higher IQ was seen with greater size at birth and greater weight gain in infancy. Also, greater growth in height and head circumference throughout the first 5 y of life was associated with higher childhood IQ whereas greater weight gain after the first year of life was not.

Diminished verbal ability among children conceived through ART with exposure to high serum estradiol in utero

PurposeHigher serum estradiol levels occur in women undergoing assisted reproductive technology (ART) owing to ovarian stimulation. Here, we investigated the association between maternal serum estradiol levels and the intellectual development of offspring conceived with ART.MethodsA total of 204 singletons born after fresh embryo transfer were recruited for this cohort study. Among them, 102 children were born from mothers with high serum estradiol levels (> 12,000 pmol/L) on the day that human chorionic gonadotropin was administered. Another 102 children, matched by gestational age and age of the children, were recruited as controls from mothers with low serum estradiol (≤ 12,000 pmol/L). The Wechsler Preschool and Primary Scale of Intelligence was used to evaluate the intellectual development of the children.ResultsChildren from mothers with higher serum estradiol levels scored lower in the verbal intelligence quotient (IQ) tests and verbal comprehension than children whose mothers had lower estradiol levels. The main difference between the two groups was in verbal subtests including information, vocabulary, and sorting. Partial correlation analysis revealed that the logarithm of maternal serum estradiol level negatively correlated with verbal IQ, performance IQ, and full scale IQ.ConclusionOur data demonstrate that a high maternal serum estradiol level may negatively associate the verbal ability of children conceived via ART.

Mechanical Ventilation Duration, Brainstem Development, and Neurodevelopment in Children Born Preterm: A Prospective Cohort Study

To determine, in children born preterm, the association of mechanical ventilation duration with brainstem development, white matter maturation, and neurodevelopmental outcomes at preschool age. This prospective cohort study included 144 neonates born at <30weeks of gestation (75 male, mean gestational age 27.1weeks, SD 1.6) with regional brainstem volumes automatically segmented on magnetic resonance imaging at term-equivalent age (TEA). The white matter maturation was assessed by diffusion tensor imaging and tract-based spatial statistics. Neurodevelopmental outcomes were assessed at 4.5years of age using the Movement Assessment Battery for Children, 2nd Edition, and the Wechsler Primary and Preschool Scale of Intelligence, 4th Edition, full-scale IQ. The association between the duration of mechanical ventilation and brainstem development was validated in an independent cohort of children born very preterm. Each additional day of mechanical ventilation predicted lower motor scores (0.5-point decrease in the Movement Assessment Battery for Children, 2nd Edition, score by day of mechanical ventilation, 95% CI -0.6 to -0.3, P<.0001). Prolonged exposure to mechanical ventilation was associated with smaller pons and medulla volumes at TEA in 2 independent cohorts, along with widespread abnormalities in white matter maturation. Pons and medulla volumes at TEA predicted motor outcomes at 4.5years of age. In neonates born very preterm, prolonged mechanical ventilation is associated with impaired brainstem development, abnormal white matter maturation, and lower motor scores at preschool age. Further research is needed to better understand the neural pathological mechanisms involved.

Global DNA methylation and cognitive and behavioral outcomes at 4 years of age: A cross-sectional study.

BackgroundAccumulating evidence suggests that breastfeeding exclusivity and duration are positively associated with child cognition. This study investigated whether DNA methylation, an epigenetic mechanism modified by nutrient intake, may contribute to the link between breastfeeding and child cognition. The aim was to quantify the relationship between global DNA methylation and cognition and behavior at 4 years of age.MethodsChild behavior and cognition were measured at age 4 years using the Wechsler Preschool and Primary Scale of Intelligence, third version (WPPSI‐III), and Child Behavior Checklist (CBC). Global DNA methylation (%5‐methylcytosines (%5mC)) was measured in buccal cells at age 4 years, using an enzyme‐linked immunosorbent assay (ELISA) commercial kit. Linear regression models were used to quantify the statistical relationships.ResultsData were collected from 73 children recruited from the Women and Their Children's Health (WATCH) study. No statistically significant associations were found between global DNA methylation levels and child cognition or behavior (p > .05), though the estimates of effect were consistently negative. Global DNA methylation levels in males were significantly higher than in females (median %5mC: 1.82 vs. 1.03, males and females, respectively, (p < .05)).ConclusionNo association was found between global DNA methylation and child cognition and behavior; however given the small sample, this study should be pooled with other cohorts in future meta‐analyses.